• Molecules and Cells
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• 제37권11호
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• pp.804-811
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• 2014

The protease-activated receptor (PAR)-2 is highly expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although several mechanisms have been suggested to explain PAR-2-induced hypotension, the precise mechanism remains to be elucidated. To investigate this possibility, we investigated the effects of PAR-2 activation on N-type $Ca^{2+}$ currents ($I_{Ca-N}$) in isolated neurons of the celiac ganglion (CG), which is involved in the sympathetic regulation of mesenteric artery vascular tone. PAR-2 agonists irreversibly diminished voltage-gated $Ca^{2+}$ currents ($I_{Ca}$), measured using the patch-clamp method, in rat CG neurons, whereas thrombin had little effect on $I_{Ca}$. This PAR-2-induced inhibition was almost completely prevented by ${\omega}$-CgTx, a potent N-type $Ca^{2+}$ channel blocker, suggesting the involvement of N-type $Ca^{2+}$ channels in PAR-2-induced inhibition. In addition, PAR-2 agonists inhibited $I_{Ca-N}$ in a voltage-independent manner in rat CG neurons. Moreover, PAR-2 agonists reduced action potential (AP) firing frequency as measured using the current-clamp method in rat CG neurons. This inhibition of AP firing induced by PAR-2 agonists was almost completely prevented by ${\omega}$-CgTx, indicating that PAR-2 activation may regulate the membrane excitability of peripheral sympathetic neurons through modulation of N-type $Ca^{2+}$ channels. In conclusion, the present findings demonstrate that the activation of PAR-2 suppresses peripheral sympathetic outflow by modulating N-type $Ca^{2+}$ channel activity, which appears to be involved in PAR-2-induced hypotension, in peripheral sympathetic nerve terminals.

• Molecules and Cells
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• 제39권4호
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• pp.322-329
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• 2016

Voltage-gated $Ca^{2+}$ ($Ca_V$) channels are dynamically modulated by Gprotein-coupled receptors (GPCR). The $M_1$ muscarinic receptor stimulation is known to enhance $Ca_V2.3$ channel gating through the activation of protein kinase C (PKC). Here, we found that $M_1$ receptors also inhibit $Ca_V2.3$ currents when the channels are fully activated by PKC. In whole-cell configuration, the application of phorbol 12-myristate 13-acetate (PMA), a PKC activator, potentiated $Ca_V2.3$ currents by ~two-fold. After the PMA-induced potentiation, stimulation of $M_1$ receptors decreased the $Ca_V2.3$ currents by $52{\pm}8%$. We examined whether the depletion of phosphatidylinositol 4,5-bisphosphate ($PI(4,5)P_2$) is responsible for the muscarinic suppression of $Ca_V2.3$ currents by using two methods: the Danio rerio voltage-sensing phosphatase (Dr-VSP) system and the rapamycin-induced translocatable pseudojanin (PJ) system. First, dephosphorylation of $PI(4,5)P_2$ to phosphatidylinositol 4-phosphate (PI(4)P) by Dr-VSP significantly suppressed $Ca_V2.3$ currents, by $53{\pm}3%$. Next, dephosphorylation of both PI(4)P and $PI(4,5)P_2$ to PI by PJ translocation further decreased the current by up to $66{\pm}3%$. The results suggest that $Ca_V2.3$ currents are modulated by the $M_1$ receptor in a dual mode-that is, potentiation through the activation of PKC and suppression by the depletion of membrane $PI(4,5)P_2$. Our results also suggest that there is rapid turnover between PI(4)P and $PI(4,5)P_2$ in the plasma membrane.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.353-359
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• 1998

In gastrointestinal smooth muscle, muscarinic stimulation by carbachol (CCh) activates nonselective cation channel current ($I_{CCh}$) which is facilitated by intracellular [$Ca^{2+}$] increase. Caffeine is widely used in experiments to mobilize $Ca^{2+}$ from intracellular stores. This study shows a strong inhibitory effect of caffeine on $I_{CCh}$ in guinea-pig gastric myocyte. In this study, the underlying mechanism of the inhibitory effect of caffeine was investigated. $I_{CCh}$ was completely suppressed by the addition of caffeine (10 mM) to the superfusing solution. Inhibition of $I_{CCh}$ by caffeine was not related to the intracellular cAMP accumulation which was expected from the phosphodiesterase-inhibiting effect of caffeine. The blockade of $InsP_3-induced$ $Ca^{2+}$ release by heparin had no significant effects on the activation of $I_{CCh}$. When the same cationic current had been induced by intracellular dialysis of $GTP[{\gamma}S]$ in order to bypass the muscarinic receptor, the inhibitory effect of caffeine was significantly attenuated. The results of this study indicate that both intracellular signalling pathways for $I_{CCh}$, proximal and distal to G-protein activation, are suppressed by caffeine. A major inhibition was observed at the proximal level.

• The Korean Journal of Physiology and Pharmacology
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• 제13권6호
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• pp.437-442
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• 2009

A non-steroidal anti-inflammatory drug (NSAID) has many adverse effects including cardiovascular (CV) risk. Diclofenac among the nonselective NSAIDs has the highest CV risk such as congestive heart failure, which resulted commonly from the impaired cardiac pumping due to a disrupted excitationcontraction (E-C) coupling. We investigated the effects of diclofenac on the L-type calcium channels which are essential to the E-C coupling at the level of single ventricular myocytes isolated from neonatal rat heart, using the whole-cell voltage-clamp technique. Only diclofenac of three NSAIDs, including naproxen and ibuprofen, significantly reduced inward whole cell currents. At concentrations higher than $3\;{\mu}M$, diclofenac inhibited reversibly the $Na^+$ current and did irreversibly the L-type $Ca^{2+}$ channels-mediated inward current $(IC_{50}=12.89\pm0.43\;{\mu}M)$ in a dose-dependent manner. However, nifedipine, a well-known L-type channel blocker, effectively inhibited the L-type $Ca^{2+}$ currents but not the $Na^+$ current. Our finding may explain that diclofenac causes the CV risk by the inhibition of L-type $Ca^{2+}$ channel, leading to the impairment of E-C coupling in cardiac myocytes.

• 유기물자원화
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• 제28권4호
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• pp.43-52
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• 2020

멤브레인을 이용한 기체 분리 기술이 발전함에 따라 분리 과정을 설명하기 위해 다양한 수학적 모델을 개발하고 적용해 왔다. 본 연구에서는 셀룰로오스 아세테이트(CA) 중공사 분리막을 제조하여 실험에 사용하였다. 메탄, 질소, 산소 및 이산화탄소 순수가스를 이용하여 투과도를 측정하고, 향류 흐름 모델(Counter-current model)을 적용하여 실험데이터와 비교/해석하였다. CA 막에 대한 이산화탄소와 메탄의 투과도는 각각 25.82 GPU와 0.65 GPU로 나타났다. CO2/CH4 선택도는 39.7이었다. 순수가스 테스트 후 세 가지 모의 혼합가스에 대한 분리 테스트를 수행하였으며, 다양한 stage-cut 조건에서 투과된 가스의 농도를 측정하였다. 실험으로 얻은 데이터를 향류 흐름 모델로 비교한 결과 상당히 일치하는 것으로 나타났으며, CA 멤브레인 모듈을 사용한 바이오가스 분리를 수학적 모델로 구현할 수 있었다. 또한 유한차분법(FDM)을 적용하여 멤브레인에서 바이오가스의 분리 거동을 유추할 수 있었다. 향후 향류 흐름 모델은 바이오가스 분리 공정을 위한 모델로서 활용 가능할 것으로 기대된다.

• The Korean Journal of Physiology and Pharmacology
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• 제16권5호
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• pp.343-348
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• 2012

Blocking or regulating $K^+$ channels is important for investigating neuronal functions in mammalian brains, because voltage-dependent $K^+$ channels (Kv channels) play roles to regulate membrane excitabilities for synaptic and somatic processings in neurons. Although a number of toxins and chemicals are useful to change gating properties of Kv channels, specific effects of each toxin on a particular Kv subunit have not been sufficiently demonstrated in neurons yet. In this study, we tested electro-physiologically if heteropodatoxin2 ($HpTX_2$), known as one of Kv4-specific toxins, might be effective on various $K^+$ outward currents in CA1 neurons of organotypic hippocampal slices of rats. Using a nucleated-patch technique and a pre-pulse protocol in voltage-clamp mode, total $K^+$ outward currents recorded in the soma of CA1 neurons were separated into two components, transient and sustained currents. The extracellular application of $HpTX_2$ weakly but significantly reduced transient currents. However, when $HpTX_2$ was added to internal solution, the significant reduction of amplitudes were observed in sustained currents but not in transient currents. This indicates the non-specificity of $HpTX_2$ effects on Kv4 family. Compared with the effect of cytosolic 4-AP to block transient currents, it is possible that cytosolic $HpTX_2$ is pharmacologically specific to sustained currents in CA1 neurons. These results suggest that distinctive actions of $HpTX_2$ inside and outside of neurons are very efficient to selectively reduce specific $K^+$ outward currents.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.361-368
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• 1998

The spontaneous contractions of gastric smooth muscles are regulated by slow waves, which are modulated by both nervous system and humoral agents. This study was designed to examine the effects of prostaglandin $E_2$ ($PGE_2$) on the contractile and electrical activities of antral smooth muscles in guinea-pig stomach, using an intracellular recording technique. To elucidate the underlying mechanism for its effect on contractility, ionic currents were also measured using a whole-cell patch clamp method. The basal tone by $PGE_2$ was variable, whereas the magnitude of phasic contractions was reduced ($19.0{\pm}2.1%$, n=19). The resting membrane potentials were hyperpolarized ($-4.4{\pm}0.5%$ mV, n=10), and plateau potentials were lowered ($-2.9{\pm}0.5%$ mV, n=10). In most cases, however, the initial peak potentials of slow waves were depolarized more by $PGE_2$ than those of control. The frequency of the slows wave was increased from $5.7{\pm}0.2$ cycles/min to $6.5{\pm}0.2$ (n=22). Voltage-operated $Ca^{2+}$ currents were decreased by $PGE_2$ (n=5). Voltage-operated $K^+$ currents, both Ca-dependent and Ca-independent, were increased (n=5). These results suggest that $PGE_2$ plays an important role in the modulation of gastric smooth muscle activities, and its inhibitory effects on the contractility and activities of slow waves are resulted from both decrease of $Ca^{2+}$ currents and increase of $K^+$ currents.

• Nuclear Engineering and Technology
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• 제51권6호
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• pp.1540-1553
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• 2019

A nuclear power plant (NPP) is a highly complex system-of-systems as manifested through its internal systems interdependence. The negative impact of such interdependence was demonstrated through the 2011 Fukushima Daiichi nuclear disaster. As such, there is a critical need for new strategies to overcome the limitations of current risk assessment techniques (e.g. the use of static event and fault tree schemes), particularly through simulation of the nonlinear dynamic feedback mechanisms between the different NPP systems/components. As the first and key step towards developing an integrated NPP dynamic probabilistic risk assessment platform that can account for such feedback mechanisms, the current study adopts a system dynamics simulation approach to model the thermal dynamic processes in: the reactor core; the secondary coolant system; and the pressurized water reactor. The reactor core and secondary coolant system parameters used to develop system dynamics models are based on those of the Palo Verde Nuclear Generating Station. These three system dynamics models are subsequently validated, using results from published work, under different system perturbations including the change in reactivity, the steam valve coefficient, the primary coolant flow, and others. Moving forward, the developed system dynamics models can be integrated with other interacting processes within a NPP to form the basis of a dynamic system-level (systemic) risk assessment tool.

• 한국전기전자재료학회:학술대회논문집
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• 한국전기전자재료학회 2001년도 하계학술대회 논문집
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• pp.697-700
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• 2001

In this paper, the structural and electrical properties of the Sr$_{1-x}$ Ca$_{x}$TiO$_3$ (0$\leq$x$\leq$0.2) (0$\leq$r$\leq$0.2)-based grain boundary layer ceramics were investigated by X-ray, SEM and V-I system. Increasing the Ca content, the average grain size and the lattice constant were decreased. The relative density of all specimens was >96%. The 2nd phase formed by thermal diffusing from the surface lead to a very excellent electrical properties, that is, $\varepsilon$$_{r}$>50000, tan$\delta$<0.05, $\Delta$C< $\pm$ 10%.\pm$ 10%.%.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1998년도 학술발표회
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• pp.37-37
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• 1998

Effects of endothelin-l (ET-l) on contraction, $Ca^{2＋}$ transient and L -type $Ca^{2＋}$ current ( $I_{Ca,L}$) were investigated in single ventricular myocytes isolated from guinea-pig hearts. ET-l at concentrations of 5 and 10 nM produced a biphasic pattern of inotropism： a first decrease in contraction by 34.4$\pm$2.5 ％ of the control followed by a sustained increase in contraction by 66.6$\pm$8.4% (mean$\pm$S.E.M., n=9).(omitted)